Lapatinib is a pharmaceutical active ingredient used for the treatment of advanced metastatic lung cancer and it is currently available on the market under the name Tykerb® sold by GlaxoSmithKline (GSK).
According to manufacturer, Tykerb® contains Lapatinib as monohydrate ditosylate salt of formula (I-bis):
having the chemical name of N-{3-chloro-4-[(3-fluoro-benzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine bis(4-methylbenzene-sulfonate) monohydrate, CAS RN 388082-78-8 and m.p. 250-256° C.
This substance can be prepared following the teachings of the prior art such as for example those contained in U.S. Pat. No. 7,157,466. In examples 10 and 11 this reference shows the preparation of the monohydrate ditosylate salt starting from anhydrous ditosylate salt.
The main disadvantage of such methods, is that some intermediates such as for example those having an aldehyde function in free form are poorly soluble, thus leading to low productivity. In other methods stannane intermediates are used which entail problems related to the disposal of waste water.